Abstract:

Gamma-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system (CNS). Of the known receptors for GABA, the pentameric GABAA receptor appears to mediate fast GABA neurotransmission in the CNS. A number of different GABAA receptor subunits have been described to date, including α1-6, β1-3, γ1-2, and δ, with the specific functionality of any one receptor dictated by the combination of subunits. Although much is known about the pattern of GABAA subunit expression across the adult brain, the pattern of such expression during the critical developmental period of adolescence, which is a time of rapid neurobiological, hormonal, and behavioral change, remains largely unknown. GABAA receptor systems play a key role in normal neural, hormonal, and behavioral function, warranting a basic understanding of adolescent-specific alterations in the pattern of subunit expression. The current project focuses on determining the pattern of mRNA expression of GABAA receptor subunits in early adolescent (postnatal day 30) versus adult (postnatal day 65) mice. The prefrontal cortex, hippocampus, nucleus accumbens, midbrain, amygdala and cerebellum were harvested at these two ages; thus far the midbrain has been the focus due to the presence of the ventral tegmental area and its well-known role in motivation, reward and drug addiction. Midbrain tissue was processed for determination of GABAA receptor subunit mRNA expression using RT-PCR. We predict that early adolescence will be associated with a unique pattern of GABAA receptor subunit expression, suggesting an important role for GABAA receptors in the neurobiological, hormonal, and behavioral profile of this developmental period in mice. Preliminary findings indicate an increase in GABAA delta subunit expression in the adult midbrain.